Overview

Dr. Howell is a Professor of Radiology at Rutgers New Jersey Medical School. He
received his bachelor?s degree in physics in 1982 and a doctorate in 1987 from the
University of Massachusetts (Amherst). He is Chief of the Division of Radiation
Research and Chair of the Rutgers Radiation Safety Committee. Dr. Howell has authored
over 100 scientific publications on radiation dosimetry and radiobiology of internal
radionuclides, including two books and two patents. Professor Howell serves on the
Society of Nuclear Medicine?s Medical Internal Radiation Dose Committee. He has served
on committees for NCRP Report 167 Potential impact of individual genetic
susceptibility and previous radiation exposure on radiation risk for astronauts, ICRU
Report 67 Absorbed dose specification in nuclear medicine, ICRU Report 86
Quantification and reporting of low-dose and other heterogeneous exposures, and he
serves on the International Commission on Radiation Units and Measurements. He is the
recipient of the 2004 Loevinger-Berman Award from the Society of Nuclear Medicine and
New Jersey Medical School?s 2009 Basic Science Faculty of the Year Award.

Education

PHD, 1987, University of Massachusetts, Physics
B.S., 1982, University of Massachusetts

Curriculum Vitae

View CV

Relevant Publications

J. M. Akudugu and R. W. Howell, A method to predict response of cell populations to cocktails of chemotherapeutics and radiopharmaceuticals: Validation with daunomycin, doxorubicin, and the alpha particle emitter 210Po. Nucl Med Biol 39, 954-961 (2012).

J. M. Akudugu and R. W. Howell, Flow cytometry-assisted Monte Carlo simulation predicts clonogenic survival of cell populations with lognormal distributions of radiopharmaceuticals and anticancer drugs. Int J Radiat Biol 88, 286-293 (2012).

R. F. Hobbs, R. W. Howell, H. Song, S. Baechler and G. Sgouros, Redefining Relative Biological Effectiveness in the Context of the EQDX Formalism: Implications for Alpha- Particle Emitter Therapy. Radiat Res 181, 90-98 (2014).

B. Vaziri, H. Wu, A. P. Dhawan, P. Du, R. W. Howell, S. M. Committee and S. M. Committee, MIRD Pamphlet No. 25: MIRDcell V2.0 Software Tool for Dosimetric Analysis of Biologic Response of Multicellular Populations. J Nucl Med 55, 1557-1564 (2014).

J. B. Pasternack, J. D. Domogauer, A. Khullar, J. M. Akudugu and R. W. Howell, The advantage of antibody cocktails for targeted alpha therapy depends on specific activity. J Nucl Med 55, 2012-2019 (2014).

Buonanno M, De Toledo SM, Howell RW, Azzam EI. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions. Journal of radiation research (Tokyo). May 2015;56(3):502-508.

Roche M, Neti PV, Kemp FW, Azzam EI, Ferraris RP, Howell RW. High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation. Radiat Res. Oct 20 2015;184(5):470-481.

Howell RW. Physical Considerations for Understanding Responses of Biological Systems to Low Doses of Ionizing Radiation: Nucleosome Clutches Constitute a Heterogeneous Distribution of Target Volumes. Health Phys. Mar 2016;110(3):283-286.

Kemp FW, Portugal F, Akudugu JM, Neti PV, Ferraris RP, Howell RW. Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion. Health Phys. Jul 2016;111(1):52-57.

Solanki JH, Tritt T, Pasternack JB, Kim JJ, Leung CN, Domogauer JD, et al. Cellular Response to Exponentially Increasing and Decreasing Dose Rates: Implications for Treatment Planning in Targeted Radionuclide Therapy. Radiat Res 2017; 188 (2):221-234.

Areas Of Interest

Dosimetry

Drug Design

Ionizing Radiation

Nuclear Medicine

Radioimmunotherapy

Radionuclide

Therapeutics

Radiation induced bystander effects in radium-223 therapy

Despite the use of adjuvant treatments for breast cancer, it is common for patients to succumb to metastatic disease. Metastatic disease arises principally from disseminated tumor cells (DTC) that have been shed from primary tumors and localize in lymph nodes and organs such as bone marrow. DTC can progress to micrometastases through a complex series of steps. About 20% of 5-year breast cancer survivors will ultimately relapse in years 5-10 post-treatment. These recurrences often arise in bone. The presence of DTC is a significant risk factor in reducing the life-expectancy of patients. Therefore, a key goal for radionuclide therapies of cancer is to develop strategies to sterilize DTC in bone. Radium-223 dichloride, a drug that emits potent alpha particle radiation, was recently approved by the FDA for treatment of advanced metastatic prostate cancer in bone. Radium-223 binds to bone surfaces and only cancer cells that lie within the ~100 ?m range of alpha particles are irradiated directly. Yet, research has shown that irradiated cells can generate signals that cause biological changes in neighboring cells that have been hit by little or no radiation. The nature of these changes can depend on the radiation dose. Alpha particles produce the most potent of these bystander effects and cell killing can be a consequence. Therefore, bystander effects may play an important role in killing or otherwise altering the behavior of DTC that are beyond the range of the alpha particles. We hypothesize that chronic alpha-particle irradiation of bone and surrounding tissue by radium-223 causes dose-dependent bystander effects that result in reduction of proliferation, migration and invasion rates of bystander DTC in bone marrow, and increased killing of bystander DTC. In addition, we hypothesize that these bystander effects will alter the radiosensitivity of the DTC to subsequent radiotherapy treatments. We will test these hypotheses with experiments conducted with human breast cancer cells in innovative organ culture and in vivo animal models. The proposed studies are carried out in four interrelated, yet independent aims. The information gained from Aims 1 and 3 will enhance our understanding of the efficacy of radium-223 therapy and whether bystander effects play a role. It may translate into strategies that enhance its effectiveness in killing DTC. It will reveal whether non-targeted effects can be exploited with radium-223 in a clinical setting. Recognizing that the future of radium-223 therapies may ultimately evolve from palliative to front-line therapies, the experiments in Aim 2 will guide how radium-223 may impact the efficacy of subsequent radiotherapies. Importantly, Aim 4 develops novel small scale dosimetry that will make it possible to identify bystander cell populations and correlate their responses with absorbed dose rate and absorbed dose to the neighboring tissues. In summary, our efforts seek to gain knowledge in support of an expanded therapeutic role for radium-223 and alpha particle emitting radionuclides in general. Our proposed studies are in direct response to recent statements that the potential role of bystander effects in radionuclide therapies is underexplored.